Biosynthesis of granulysin, a novel cytolytic molecule

Dennis A. Hanson, Allan A. Kaspar, Francis R Poulain, Alan M. Krensky

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Granulysin is a newly described lytic molecule expressed by CTL and NK cells. Three mRNA (519, 520, and 522) and two protein products of 15 and 9 kDa are encoded by the granulysin gene. Stable transfectants overexpressing the predominate 520 mRNA were generated to determine the protein products originating from the translation of this message. A transfectant of the NK cell tumor YT overexpressed both 15 and 9 kDa proteins while a transfectant of the T cell tumor HuT78 produced mainly 15 kDa granulysin. Thus the 520 mRNA is sufficient for production of both 15 and 9 kDa granulysin. 9 kDa granulysin accumulated via post-translational processing of 15 kDa protein and was present intracellularly but not in the cell culture supernatant, indicating specific retention of the 9 kDa protein. An inhibitor of granule acidification, concanamycin A, blocked the processing of 15 kDa granulysin to the 9 kDa form. A deduced structural difference between the two forms of the protein and a decrease in lytic activity of 9 kDa granulysin at granule pH suggest two mechanisms by which a granulysin expressing cell is protected from autolysis during the biosynthesis of this potentially harmful molecule.

Original languageEnglish (US)
Pages (from-to)413-422
Number of pages10
JournalMolecular Immunology
Volume36
Issue number7
DOIs
StatePublished - May 1999
Externally publishedYes

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Proteins
Natural Killer Cells
Messenger RNA
Autolysis
Neoplasms
Cell Culture Techniques
T-Lymphocytes
Genes
concanamycin A

Keywords

  • Biochemistry
  • CTL
  • Cytolytic granules
  • NK cells

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

Biosynthesis of granulysin, a novel cytolytic molecule. / Hanson, Dennis A.; Kaspar, Allan A.; Poulain, Francis R; Krensky, Alan M.

In: Molecular Immunology, Vol. 36, No. 7, 05.1999, p. 413-422.

Research output: Contribution to journalArticle

Hanson, Dennis A. ; Kaspar, Allan A. ; Poulain, Francis R ; Krensky, Alan M. / Biosynthesis of granulysin, a novel cytolytic molecule. In: Molecular Immunology. 1999 ; Vol. 36, No. 7. pp. 413-422.
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